AAV, a non-pathogenic, helper-dependent virus, is an attractive vector for gene therapy as it exhibits a wide host and tissue range and is able to replicate in cells from any species as long as there is a successful infection of such cells with a suitable helper virus [e.g., Adenovirus (Ad) or Herpesvirus]. The host and tissue tropism of AAV is determined by the ability of its capsid to bind to specific cellular receptors and/or co-receptors. Due to the broad host and tissue range, however, delivery of conventional AAV preferentially to a particular tissue of interest has been problematic.
AAV of several different serotypes are known. Of these, serotype 2 AAV has been the most extensively studied and characterized. Accordingly, serotype 2 rAAV vectors (i.e., nucleic acid constructs) and virions (i.e., encapsidated vectors) have been proposed as the vector of choice for gene transfer protocols. Animal experiments, however, have shown that dramatic differences exist in the transduction efficiency and cell specificity of rAAV virions of different serotypes (Chao et al., Mol. Ther. 2:619–623, 2000; Davidson et al., PNAS 97:3428–3432, 2000; and Rabinowitz et al., J. Virol. 76:791–801, 2002). For example, non-serotype 2 AAV virions were able to transduce certain tissues more efficiently and specifically than serotype 2 virions. Accordingly, an AAV virion including a well-characterized serotype 2 genome and a non-serotype 2 capsid would be useful for certain tissue-specific gene transfer applications. Methods that facilitate preparing such pseudotyped AAV virions would also be useful. Current methods involve the use of multiple vectors to provide the replication, packaging, and helper functions that are required for the formation of recombinant virions. These methods are inefficient and inadequate for large-scale production of pseudotyped recombinant virions.